tbuckley/cabot-search huggingface dataset:
Abstract P3-09-02: Pateint Derived Breast Cancer Organoids as a Model for Testing Personalized Therapies
Authors: Nadeem Wajih, Richard Erali, Steven Forsythe, Shay Soker, Konstantinos Votanopoulos
Journal: Cancer Research (2023)

Abstract Introduction: Breast cancer is one of the most frequently diagnosed cancer in women with a high mortality rate. More than 20 different subtypes of breast cancer are identified. Advancement in patient-derived organoid technology makes it possible to preserve cellular, structural, and tissue microenvironment which mimics the tissue in vivo. Method: We developed patient derived breast organoids both from normal and cancer biopsies recapitulate the structure of breast tissue. Breast biopsies were enzymatically digested to yield a single cell suspension. About 1 × 105 cells were encapsulated in a specialized hydrogel mixture. Immune enhanced breast tumor organoids (iTOs) included 2 × 105 patient matched PMBCs. Results: Histological analyses of the breast organoids shows the characteristics of the breast tissue with well-defined acini in H&amp;E. In tumor organoids acini were somewhat perturbed compared to normal breast organoids. Immuno-fluorescence staining shows the expression of breast biomarkers including EGF receptor 2 (HER2), Progesterone receptor (PR), Estrogen receptor (ER). Zona occludin 1 and 2 and keratin 19 expression in luminal cells and expression of Keratin 14 and P63 in basal cells suggested correct polarization in the organoids. Immunofluorescence staining of (iTOs), with T cell markers including CD3, CD4, and CD8 indicated that immune cells remained viable in the iTOs. Drug responses to Doxorubicin, Paclitaxel and a combination of Doxorubicin-Paclitaxel showed significant inhibition of cell growth in normal and tumor organoids (p&amp;lt; 0.04, n=11) except for Paclitaxel failed to inhibit tumor cell growth. However, immunotherapy with nivolumab (anti PD-1) showed no significant effect on cell growth. Conclusions: Pateint Derived Breast cancer organoids recapitulate the histological features of breast tissue in culture and response to chemotherapies. In the future, patient-derived tumor organoids can provide a platform for personalized medicine. Citation Format: Nadeem Wajih, Richard Erali, Steven Forsythe, Shay Soker, Konstantinos Votanopoulos. Pateint Derived Breast Cancer Organoids as a Model for Testing Personalized Therapies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-09-02.
Associations of childhood-to-adulthood body size trajectories and genetic susceptibility with the risks of osteoarthritis: a population-based cohort study of UK Biobank data
Authors: Muhui Zeng, Shibo Chen, Tianxiang Fan, Hao Yang, Peihua Cao, Zhiqiang Wang, Yujie Zhang, Yan Zhang, David Hunter, Qian Yang, Changhai Ding, Zhaohua Zhu
Journal: The Lancet Global Health (2023)

BackgroundLarge adulthood body size was associated with increased risk of osteoarthritis. We aimed to examine the association between body size trajectories from childhood to adulthood and potential interactions with genetic susceptibility on osteoarthritis risk.MethodsWe included participants from the UK Biobank aged 38–73 years in 2006–10. Childhood body size information was collected by questionnaire. Adulthood BMI was assessed and transformed into three categories (<25 kg/m2 for normal, 25–29·9 kg/m2 for overweight, and >30 kg/m2 for obesity). A Cox proportional hazards regression model was applied to assess the association between body size trajectories and osteoarthritis incidence. Osteoarthritis-related polygenic risk score (PRS) was constructed to evaluate its interactions with body size trajectories on osteoarthritis risk.FindingsFor the 466 292 participants included, we identified nine body size trajectories [thinner to normal (11·6%), overweight (17·2%), or obesity (26·9%); average to normal (11·8%), overweight (16·2%), or obesity (23·7%); and plumper to normal (12·3%), overweight (16·2%), or obesity (23·6%)]. Compared with individuals in the average-to-normal group, all other trajectory groups had higher risks of osteoarthritis, after adjustment for demographic, social-economic and lifestyle covariates (hazard ratios [HRs] 1·05–2·41; all p<0·01). Among them, thinner-to-obesity (HR 2·41; 95% CI 2·23–2·49) had the most prominent association with increased osteoarthritis risk. A high PRS was significantly associated with an increased risk of osteoarthritis (1·14; 1·11–1·16), whereas no interaction between childhood-to-adulthood body size trajectories and PRS on osteoarthritis risks was observed. The population attributable fraction suggested that body size towards normal in adulthood could eliminate osteoarthritis cases by 18·67% for thinner-to-overweight to 38·74% for plumper-to-obesity.InterpretationAverage-to-normal body size seems to be the healthiest childhood-to-adulthood trajectory for osteoarthritis risk, whereas a trajectory of increased body size from thinner to obesity has the highest risk for osteoarthritis. These associations are independent of osteoarthritis genetic susceptibility.FundingThe National Natural Science Foundation of China (32000925) and Guangzhou Science and Technology Program (202002030481).
Abstract P3-01-01: Unicentric experience with icdk4/6 in metastatic breast cancer
Authors: Fernando Henao, Esteban Nogales Fernández, Lourdes Sevilla Ortega, Ruben De Toro Salas, Natalia Palazón Carrión, Maria del Carmen Álamo de la Gala, Alberto Sanchez-Camacho Mejías, Maria Luisa Sanchez Leon, Luis de la Cruz-Merino
Journal: Cancer Research (2023)

Abstract Currently, the standard of care for luminal metastatic breast cancer is the combination of cyclin inhibitors with hormone therapy. Palbociclib and Ribociclib have been approved for marketing since 2017 and Abemaciclib since 2019 in Spain. In our center we have experience with the three cdk 4/6 inhibitors in different lines of treatment and patient profiles. We gather in the present work the unicentric experience with the three icdk 4/6. We have collected a total of 152 patients treated with the different cyclin inhibitors, achieving median PFS of 32.1 months for Palbociclib, 28.6 months for Ribociclib and 18.4 months for Abemaciclib. Overall survival data is still immature. The context of the patient and the disease has a significant impact on the results, as well as the line of treatment used. The toxicity profile of the three drugs does not differ from what the registry trials describe, with neutropenia being the most common side effect. We also describe dose reductions produced by the three icdk4/6. Conclusions: This is a real-life study with experience in a single center with the three icdk4/6 currently marketed with a cohort of more than 150 patients. We present data that conform to what was reported by the clinical trials PALOMA, MONALEESA and MONARCH. The data will be updated on the date of the congress for its presentation. Citation Format: Fernando Henao, Esteban Nogales Fernández, Lourdes Sevilla Ortega, Ruben De Toro Salas, Natalia Palazón Carrión, Maria del Carmen Álamo de la Gala, Alberto Sanchez-Camacho Mejías, Maria Luisa Sanchez Leon, Luis de la Cruz-Merino. Unicentric experience with icdk4/6 in metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-01.
Abstract P3-05-37: Influence of Clinical Heterogeneity on Pregnancy Associated Breast Cancer survival: Systematic Review with Metanalysis
Authors: MARCELO ANTONINI, BARROS T. TAIS, JULIANA M. REAL, REGINALDO G. COELHO LOPES, ODAIR FERRARO, ANDRE MATTAR, LUCAS OKUMURA
Journal: Cancer Research (2023)

Abstract Objective: Pregnancy-associated breast cancer (PABC) is defined as diagnosed during pregnancy or within one year of childbirth, in which current evidence associates with poor prognosis, without showing what clinical characteristics could impact in survival. We aim to explore the impact of heterogeneity in risks on death and disease relapse, suggesting clinical characteristics that might improve PABC clinical outcomes. Methods: Medline, Embase, Cochrane, Lilacs and congress abstracts published since 2000 were used as data sources. Two reviewers independently selected manuscripts and extracted data and a third reviewer solved discrepancies. The primary outcome was overall survival (death), and secondary outcome was disease-free survival (death or relapse). Summarized hazard ratios were recalculated based on reported data. All metaanalyses used a random-effects model and heterogeneity was reported using the I2 method. Results: A total of 7143 studies were identified and 30 studies were included for metaanalyses. PABC is associated with a 96% (HR=1.96, 95%CI 1.58;2.35) higher risk of death and an additional 82% (HR=1.82, 95%CI 1.45;2.20) risk of death or disease relapse in comparison to a population of non-PABC or nulliparous BC. Through sensitivity analyses, we identified that clinical outcomes was impacted, possibly due to Ki-67 levels, poorly differentiated tumors, and triple negative breast cancer (TNBC) frequency in the study. Conclusions: PABC is correlated with poorer prognosis, suggesting that besides early diagnosis, Ki-67 levels, poorly differentiated tumors and TNBC might be relevant sources of inconsistency. So, such clinical sources of heterogeneity should be better investigated regarding the potential to evaluate alternative therapeutic strategies. PABC deaths compared to non-PABC population, represented as hazard ratio PABC deaths or disease relapse compared to non-PABC population, represented as hazard ratio Citation Format: MARCELO ANTONINI, BARROS T. TAIS, JULIANA M. REAL, REGINALDO G. COELHO LOPES, ODAIR FERRARO, ANDRE MATTAR, LUCAS OKUMURA. Influence of Clinical Heterogeneity on Pregnancy Associated Breast Cancer survival: Systematic Review with Metanalysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-37.
Abstract P4-03-03: Elevated Risk of Breast Cancer Diagnosis in Women with Dense Breasts reflects a similarly Elevated Risk of Breast Cancer Onset that is Robust to the Effect of Density on Mammography Sensitivity
Authors: Jane M. Lange, Charlotte Gard, Ellen O’meara, Ruth Etzioni
Journal: Cancer Research (2023)

Abstract Dense breasts are associated with a higher risk of breast cancer diagnosis, which has impacted risk prediction tools and patient notification policies. However, given that mammography is less sensitive for women with dense breasts and these women may be subject to different confirmation testing pathways, the true association between breast density and cancer risk is unknown. We investigated the relationship between breast density and onset using a natural history model that accounts for differential sensitivity and rates of exams by breast density. Data consisted of Breast Cancer Surveillance Consortium mammogram and cancer outcomes among women aged 40-54 with a first digital mammogram between 2000-2018 (N=33,542). Of these, 15,092 had non-dense (almost entirely fatty or scattered fibroglandular densities) and18,450 had dense (heterogeneously dense or extremely dense) breasts. We estimated the empirical sensitivity of mammograms in dense and non-dense breasts (fraction of diagnosed cancers that were screen detected) and examined rates of mammograms by density. We estimated the relative risk of breast cancer diagnosis five years after the first exam using Kaplan Meier methods and the relative risk of breast cancer onset from a natural history model, assuming density-specific sensitivity was equal to the empirical sensitivity. Empirical sensitivity was .88 in women with non-dense and .78 in women with dense breasts. Mammogram utilization was somewhat higher in women with dense breasts (HR for subsequent mammograms 1.10 (95% CI [1.07, 1.12]). The relative risk of diagnosis for dense versus non-dense breasts was 1.80 (95% CI [1.46,2.57]); based on the natural history model the relative risk of onset was 1.73 [1.43,2.25]. The estimated relative risk of onset ranged from 1.67 to 2.03 under assumptions that the relative sensitivity of the screening episode for dense versus non-dense breasts was 1.0 to 0.4. In conclusion, the association of risk of breast cancer onset with breast density is robust to assumptions about the relative sensitivity in dense and non-dense breasts. Citation Format: Jane M. Lange, Charlotte Gard, Ellen O’meara, Ruth Etzioni. Elevated Risk of Breast Cancer Diagnosis in Women with Dense Breasts reflects a similarly Elevated Risk of Breast Cancer Onset that is Robust to the Effect of Density on Mammography Sensitivity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-03.
Abstract P3-05-23: Pathological complete response rate and disease-free survival after neoadjuvant chemotherapy in patients with HER2-low and HER2-0 breast cancers
Authors: Alexandre de Nonneville, Gilles HOUVENAEGHEL, Monique Cohen, Laura SABIANI, Marie BANNIER, Frederic VIRET, Anthony Gonçalves, François BERTUCCI
Journal: Cancer Research (2023)

Abstract ABSTRACT Background: Half of HER2-negative breast cancers (BC) show HER2-low expression. The strong efficacy of recent anti-HER2 antibody-drug conjugates (ADC) in HER2-low tumors has risen the interest of HER2-low as a proper BC subtype. Chemosensitivity and prognosis of this subtype are not clear when compared to HER2-0 tumors. We investigated the pathological complete response (pCR) and disease-free survival (DFS) rates in BC patients receiving neoadjuvant chemotherapy for HER2-low or HER2-0 tumors. Methods: Data were collected from the Institut Paoli-Calmettes European Comprehensive Cancer Center database. HER2-low tumors were defined by HER2 IHC score of 1+ or 2+ with negative FISH, and HER2-0 by IHC score of 0+. Clinicopathological characteristics, pCR (defined as [ypT0/ypTis] and [pN0sn or ypN0]) and DFS rates were compared between the two cohorts. Results: From Jan/2005 to Jun/2021, 1,111 patients receiving neoadjuvant chemotherapy were evaluable. The incidence of HER2-low was 41%, including 63% of hormone receptor (HR)-positive and 37% of HR-negative tumors (p&amp;lt; 0.001). In the whole population, the pCR rate was lower in HER2-low (23%) versus HER2-0 (30%) tumors (p=0.013), but this association was lost in multivariate analysis. In HR-positive patients, HER2-low negatively impacted pCR rates when compared to HER2-0 (10% vs. 16%, p=0.046), but not in HR-negatives (46% vs. 42%), and this result was maintained in multivariate analysis (OR 0.60 [95CI 0.36-1.00]; p=0.049, and OR 1.15 [95CI 0.77-1.71]; p=0.490, respectively. No correlation existed between DFS and HER2-status. Conclusion: HER2-low is associated with HR positivity. HER2 status did not impact pCR in HR-negative patients, whereas HER2-low was associated with lower pCR rate in HR-positive patients, supporting the development of anti-HER2 ADC in this setting. Citation Format: Alexandre de Nonneville, Gilles HOUVENAEGHEL, Monique Cohen, Laura SABIANI, Marie BANNIER, Frederic VIRET, Anthony Gonçalves, François BERTUCCI. Pathological complete response rate and disease-free survival after neoadjuvant chemotherapy in patients with HER2-low and HER2-0 breast cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-23.
Abstract P2-26-14: CDK4/6 inhibitors modulate the ubiquitin–proteasome pathway in ER+ breast cancer by downregulation of UBE2C/S/T
Authors: Chih-Yi Lin, Chung-Jen Yu, Chun-Yu Liu, Ta-Chung Chao, Chi-Cheng Huang, Ling-Ming Tseng, Jiun-I Lai
Journal: Cancer Research (2023)

Abstract Despite significant improvement in therapeutic development in the past decades, breast cancer remains a formidable cause of death for women worldwide. The hormone positive subtype (HR(+)) (also known as luminal type) is the most prevalant category of breast cancer, comprising ~70% of patients. The clinical success of the three CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib has revolutionized the treatment of choice for metastatic HR(+) breast cancer. Accumulating evidence demonstrate that the properties of CDK4/6 inhibitors extend beyond inhibition of the cell cycle, including modulation of immune function, sensitizing PI3K inhibitors, metabolism reprogramming, kinome rewiring, modulation of the proteosome, and many others. The ubiquitin–proteasome pathway (UPP) is a crucial cellular proteolytic system that maintains the homeostasis and turnover of proteins. By transcriptional profiling of the HR(+) breast cancer cell lines MCF7 and T47D treated with Palbociclib, we have uncovered a novel mechanism that demonstrate the CDK4/6 inhibitors suppress the expression of three ubiquitin conjugating enzymes UBE2C, UBE2S, UBE2T. Further validation in the HR(+) cell lines show that Palbociclib and ribociclib decrease UBE2C at both the mRNA and protein level, but this phenomenon was not shared with abemaciclib. These three E2 enzymes modulate several E3 ubiquitin ligases, including the APC/C complex which plays a role in G1/S progression. We further demonstrate the UBE2C/UBE2T expression levels are associated with breast cancer survival, and HR(+) breast cancer cells demonstrate dependence on the UBE2C. Our study suggests a novel link between CDK4/6 inhibitor and UPP pathway, adding to the potential mechanisms of their clinical efficacy in cancer. Citation Format: Chih-Yi Lin, Chung-Jen Yu, Chun-Yu Liu, Ta-Chung Chao, Chi-Cheng Huang, Ling-Ming Tseng, Jiun-I Lai. CDK4/6 inhibitors modulate the ubiquitin–proteasome pathway in ER+ breast cancer by downregulation of UBE2C/S/T [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-14.
Interventions to reduce and prevent childhood obesity in low-income and middle-income countries: a systematic review and meta-analysis
Authors: Isaac Olufadewa, Miracle Adesina, Ruth Oladele, Toluwase Olufadewa, Abimbola Solagbade, Olajumoke Ogundele, Oluwadara Asaolu, Tejumade Adene, Omotayo Oladesu, Eyitayo Lawal, Joshua Nnatus, Deborah Akinrinde, Esther Opone
Journal: The Lancet Global Health (2023)
Abstract P6-01-41: Influence of HER2 expression status in the distribution of recurrence score from the OncotypeDx assay among women with early-stage estrogen-receptor-positive/HER2-negative breast cancer
Authors: Anish Shah, Pravash Budhathoki, Suman Gaire, Utsav Joshi, Siddhartha Yadav
Journal: Cancer Research (2023)

Abstract BACKGROUND: The OncotypeDX assay analyzes the expression of 21 genes, including HER2 and Grb7, to assess the predictive effect of chemotherapy in breast cancer recurrence among women with early-stage estrogen-receptor (ER) positive/HER2-negative breast cancer. In this study, we evaluate the distribution of recurrence score from the OncotypeDX assay based on the HER2 expression status by immunohistochemistry (IHC). METHODOLOGY: Utilizing the National Cancer Database, we identified adult women with a diagnosis of stage I – III ER+/HER2- invasive ductal carcinoma of the breast between the years 2010 and 2018. Recurrence scores were classified into low (&amp;lt; 11), intermediate (11-26), and high risk (&amp;gt;26); and the distribution of these recurrence scores cross-tabulated with different IHC scores of HER2 expression (0, 1+, and 2+) by IHC. Women with an IHC score of 2+ had to be negative for HER2 gene amplification by FISH. Multivariate logistic regression model adjusting for age, race, origin, progesterone receptor status, grade, and cancer stage was used to assess the odds of receiving a high OncotypeDx Score (≥26). RESULT: Among 198,931 women with ER+/HER2 negative breast cancer, 59,632 (30.0%) had HER2 IHC score of 0, 102,170 (51.4%) had IHC score of 1+, and 37,129 (18.6%) women were with IHC score of 2+. The median age at diagnosis of breast cancer among all three categories of HER2 expression was 59 years. The median recurrence score for women with IHC scores of 0,1+, and 2+ was 15, 15, and 16 respectively (p &amp;lt; 0.001). A higher proportion of women with HER2 IHC score of 2+ had a high recurrence score compared to women with an IHC score of 0 (15.2% vs. 13%, p &amp;lt; 0.001). In multivariate analysis, compared to women with HER2 IHC score of 0, women with HER2 IHC score of 2+/FISH negative were observed to have higher Odds (OR: 1.16; 95% CI: 1.11 – 1.20, p &amp;lt; 0.001) of receiving high recurrence score. There was no significant difference in the odds of receiving a high recurrence score between women with IHC 0+ and 1+(OR: 0.99; 95% CI: 0.96 – 1.03, p 0.82). CONCLUSION: Women with a HER2 IHC score of 2+ were observed to have a higher odds of receiving high-risk recurrence scores as compared to women with IHC score of 0. This needs to be further correlated with the response to chemotherapy and the risk of recurrence. Citation Format: Anish Shah, Pravash Budhathoki, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Influence of HER2 expression status in the distribution of recurrence score from the OncotypeDx assay among women with early-stage estrogen-receptor-positive/HER2-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-41.